QTL Mapping of Impulsivity-related Traits Before and After a Stressful Life Chang

描述（由申请人提供）：冲动是大量精神疾病和心理社会问题的关键特征，包括双相情感障碍、注意缺陷多动障碍、品行障碍、酗酒和药物滥用。在确定数量性状位点（QTL）和候选基因方面进展缓慢，这些基因对冲动相关疾病的脆弱性具有一致和显著的影响。需要新的和更合适的动物模型来加强目前的人类研究，以在这一重要的研究领域取得进展。拟议的研究将利用强大的马鞭草研究群体（VRC）的谱系和最近开发的马鞭草遗传连锁图谱和基因组工具，以确定数量性状基因座（QTL）的可靠和验证的行为措施的冲动相关的性状在非人灵长类动物模型。VRC谱系在一个复杂的大家族中包含多达5代的表型个体。将使用vervet微卫星连锁图对多达735名受试者的社会冲动性、攻击性、新奇寻求性、焦虑、活动性和社交性指数进行方差分量QTL分析。对感兴趣的性状的推定QTL的发现将采用SNP标记对连锁区域进行高密度作图。这将是第一个在非人类灵长类动物模型中对冲动性疾病的客观测量、定量行为内在表型进行的全基因组研究。这项研究还将提供一个独特的机会，研究环境的影响，在检测易感基因座的比较结果，在两个不同的环境中的行为性状的QTL分析，之前和之后的压力生活的变化。在越野运输和将VRC重新安置到新机构（处理和干预更频繁）后，将对450只动物样本重复进行社交冲动、攻击性、新奇寻求、焦虑、活动和社交性的行为评估。转移将使我们能够比较在基线和更紧张的环境条件下的QTL分析结果，以确定相同的冲动相关性状的环境特异性QTL。这是一种评价基因-环境交互作用在测量遗传变异对行为性状影响中的作用的新方法

DESCRIPTION (provided by applicant): Impulsivity is a key feature of a large number of psychiatric disorders and psychosocial problems, including bipolar disorder, attention deficit hyperactivity disorder, conduct disorder, alcoholism, and substance abuse. Progress has been slow in identifying quantitative trait loci (QTL) and candidate genes that have consistent and significant effects on vulnerability for impulsivity-related disorders. New and more appropriate animal models are needed to augment current human studies to make progress in this important area of study. The proposed research will take advantage of the powerful Vervet Research Colony (VRC) pedigree and the recently developed vervet genetic linkage map and genomic tools to identify quantitative trait loci (QTL) for reliable and validated behavioral measures of impulsivity-related traits in a nonhuman primate model. The VRC pedigree contains up to 5 generations of phenotyped individuals in a single complex extended family. Variance components QTL analyses will be conducted on indices of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity, and Sociability for samples of up to 735 subjects using the vervet microsatellite linkage map. The discovery of putative QTL for the traits of interest will be followed up with high density mapping of the linkage region using SNP markers. This will be the first genome wide study of objectively measured, quantitative behavioral endophenotypes for impulsivity disorders in a nonhuman primate model. This study will also provide a unique opportunity to study the influence of the environment in the detection of susceptibility loci by comparing results from QTL analysis of behavioral traits in two different environments, before and after a stressful life change. Behavioral assessments of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity and Sociability will be repeated for a sample of 450 animals following cross country transport and relocation of the VRC to a new facility with more frequent handling and interventions. The transfer will allow us to compare the results of QTL analyses under baseline and more stressful environmental conditions to identify environment-specific QTL for the same impulsivity-related traits. This is a novel way of assessing the role of the gene-environment interactions in measuring effects of genetic variation on behavior traits